10-99955492-T-C

Position:

chr10-99955492-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_015221.4(DNMBP):c.1982A>G(p.Lys661Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00875 in 1,600,692 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0060 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 84 hom. )

Consequence

DNMBP
NM_015221.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.366

Variant links:

Genes affected

DNMBP (HGNC:30373): (dynamin binding protein) This gene encodes a protein belonging to the guanine nucleotide exchange factor family, and which regulates the configuration of cell junctions. It contains multiple binding sites for dynamin and thus links dynamin to actin regulatory proteins. Polymorphisms in this gene have been linked to Alzheimer's disease in some populations, though there are conflicting reports of such linkages in other populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

DNMBP links:

DNMBP-AS1 (HGNC:20431): (DNMBP antisense RNA 1)

DNMBP-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036566257).

BP6

Variant 10-99955492-T-C is Benign according to our data. Variant chr10-99955492-T-C is described in ClinVar as [Benign]. Clinvar id is 3034405.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
DNMBP	NM_015221.4 linkuse as main transcript	c.1982A>G	p.Lys661Arg	missense_variant	4/17	ENST00000324109.9
DNMBP-AS1	NR_024130.3 linkuse as main transcript	n.177-182T>C		intron_variant, non_coding_transcript_variant
DNMBP	XM_011539559.3 linkuse as main transcript	c.1982A>G	p.Lys661Arg	missense_variant	5/18
DNMBP	XM_047424910.1 linkuse as main transcript	c.1982A>G	p.Lys661Arg	missense_variant	5/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNMBP	ENST00000324109.9 linkuse as main transcript	c.1982A>G	p.Lys661Arg	missense_variant	4/17	1	NM_015221.4	P1	Q6XZF7-1
DNMBP-AS1	ENST00000661385.1 linkuse as main transcript	n.223-990T>C		intron_variant, non_coding_transcript_variant
DNMBP-AS1	ENST00000434409.2 linkuse as main transcript	n.173-182T>C		intron_variant, non_coding_transcript_variant		2
DNMBP-AS1	ENST00000661150.1 linkuse as main transcript	n.177-1297T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00598

AC:

910

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00982

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00953

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00523

AC:

1263

AN:

241364

Hom.:

AF XY:

0.00553

AC XY:

721

AN XY:

130334

show subpopulations

Gnomad AFR exome

AF:

0.00168

Gnomad AMR exome

AF:

0.00435

Gnomad ASJ exome

AF:

0.000110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00109

Gnomad NFE exome

AF:

0.00933

Gnomad OTH exome

AF:

0.00744

GnomAD4 exome

AF:

0.00904

AC:

13093

AN:

1448454

Hom.:

Cov.:

AF XY:

0.00875

AC XY:

6290

AN XY:

719104

show subpopulations

Gnomad4 AFR exome

AF:

0.00155

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.000237

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00147

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.00635

GnomAD4 genome

AF:

0.00598

AC:

910

AN:

152238

Hom.:

Cov.:

AF XY:

0.00521

AC XY:

388

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00981

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.00953

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00806

Hom.:

Bravo

AF:

0.00635

TwinsUK

AF:

0.0108

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.00471

AC:

572

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNMBP-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 22, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.3

DANN

Benign

0.97

DEOGEN2

Benign

0.019

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.85

REVEL

Benign

0.051

Sift

Benign

0.26

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.018

MVP

0.37

MPC

0.11

ClinPred

0.011

GERP RS

-4.5

Varity_R

0.055

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over